New Blood Test Study Reveals Higher Alzheimer's Disease Prevalence in Older Populations

Alzheimer's disease represents one of the most significant global health challenges of our time, yet accurate estimates of its true prevalence in community populations have remained elusive. Traditional diagnostic methods like cerebrospinal fluid analysis and PET imaging have been too invasive or expensive for large-scale population studies. However, a groundbreaking study from Norway has leveraged new blood-based biomarker technology to provide unprecedented insights into Alzheimer's disease neuropathological changes (ADNCs) across age groups. The findings, published in Nature, reveal surprising patterns that challenge previous estimates and have significant implications for healthcare planning and treatment strategies.

The HUNT Study: A Population-Based Approach

The research utilized data from the Trøndelag Health (HUNT) study, a comprehensive population-based health survey conducted in Norway. This study included 11,486 blood samples from participants aged 58 years and older, making it the largest population-based investigation of Alzheimer's disease pathology to date. The cohort comprised 2,537 individuals aged 58-69.9 years from HUNT3 and 8,949 individuals aged 70 years and older from HUNT4, with standardized clinical assessments for dementia and mild cognitive impairment conducted in the older group.

The study's methodology represents a significant advancement in Alzheimer's research. Researchers measured plasma phosphorylated tau at threonine 217 (pTau217) using a validated commercial assay. This blood-based biomarker serves as a surrogate marker for Alzheimer's disease neuropathological changes, offering a minimally invasive alternative to traditional diagnostic methods. The assay used established cut-off values to categorize participants as ADNC negative, intermediate, or positive, providing a scalable approach to assessing Alzheimer's pathology in large populations.

Key Findings: Age-Related Prevalence Patterns

The study revealed a striking age-dependent increase in Alzheimer's disease pathology. Among participants aged 58-69.9 years, less than 8% showed evidence of ADNCs. This proportion increased dramatically with age, reaching 33.4% in those aged 70 years and older, and peaking at 65.2% in individuals over 90 years of age. These findings suggest that Alzheimer's disease pathology becomes increasingly common as people age, with the majority of individuals over 90 showing biomarker evidence of the disease.

When examining specific clinical categories within the 70+ population, the study found that 10% had preclinical Alzheimer's disease (biomarker positive but cognitively unimpaired), 10.4% had prodromal Alzheimer's disease (biomarker positive with mild cognitive impairment), and 9.8% had Alzheimer's disease dementia. The distribution of pathology across cognitive groups revealed important patterns: ADNCs were present in 60% of people with dementia, 32.6% of those with mild cognitive impairment, and 23.5% of cognitively unimpaired individuals.

Implications for Treatment Eligibility and Healthcare Planning

One of the most significant implications of this research relates to treatment eligibility for new disease-modifying therapies. Based on current recommendations for anti-amyloid immunotherapies like lecanemab and donanemab, approximately 11% of people aged 70 years and older in the study population would potentially be eligible for treatment. This translates to substantial numbers of individuals who could benefit from these emerging therapies, highlighting the importance of accurate prevalence estimates for healthcare resource planning.

The study also revealed that ADNCs were ruled out in 41% of individuals with mild cognitive impairment and 19.4% of those with dementia based on plasma pTau217 concentrations below the lower cut-off. This finding underscores that cognitive impairment in older adults often has causes other than Alzheimer's disease, emphasizing the need for accurate differential diagnosis before initiating Alzheimer's-specific treatments.

Risk Factors and Demographic Patterns

The research identified several important risk factors associated with Alzheimer's disease pathology. Individuals with one or two APOE ε4 alleles showed significantly higher ADNC prevalence (46.4% and 64.6%, respectively) compared to those without this genetic risk factor (27.1%). Education level also emerged as a significant factor, with lower educational attainment associated with higher ADNC prevalence, particularly in older age groups. This supports the cognitive reserve hypothesis, suggesting that higher education may provide some protection against the clinical manifestation of Alzheimer's pathology.

Interestingly, the study found only minor sex differences in ADNC prevalence. While men aged 80-89 showed slightly higher rates of early-stage Alzheimer's disease (preclinical and prodromal), there were no significant sex differences in Alzheimer's disease dementia prevalence across any age group. This challenges previous reports suggesting higher Alzheimer's prevalence in women and indicates that sex differences may be more complex than previously understood.

Methodological Strengths and Limitations

The study's population-based design represents a major strength, avoiding the selection biases common in clinic-based studies. The use of a standardized, validated blood biomarker assay allowed for scalable assessment of Alzheimer's pathology across thousands of individuals. The high participation rate in the HUNT study (51.1% for HUNT4 70+) further strengthens the generalizability of the findings to similar populations.

However, the researchers acknowledge several limitations. The study population was predominantly white Norwegian, limiting generalizability to more ethnically diverse populations where Alzheimer's prevalence may differ. Medical conditions were self-reported, which may not accurately reflect true disease burden. Additionally, 13.5-27.6% of participants fell into the intermediate biomarker range, requiring further diagnostic clarification through methods like cerebrospinal fluid analysis or PET imaging.

Conclusion and Future Directions

This landmark study provides the most comprehensive population-based assessment of Alzheimer's disease pathology to date, revealing higher prevalence of Alzheimer's disease dementia in older individuals and lower prevalence of preclinical Alzheimer's in younger groups than previously estimated. The findings have immediate implications for healthcare systems preparing for the implementation of new disease-modifying therapies and highlight the importance of blood-based biomarkers in population screening and diagnosis.

As blood-based Alzheimer's biomarkers become increasingly integrated into clinical practice, studies like this will be essential for understanding the true burden of disease, identifying individuals who may benefit from emerging treatments, and planning for the healthcare needs of aging populations worldwide. The research underscores the potential of minimally invasive biomarkers to transform our understanding and management of Alzheimer's disease at both individual and population levels.